Novel combination and use

Abstract

The present invention relates to the use of one or more compounds selected from the following: caffeic acid, thymol, aspirin, benzydamine hydrochloride, diclofenac sodium, flurbiprofen, ibuprofen, indomethacin, trifluoperazine hydrochloride, chlorprothixene hydrochloride, triflupromazine hydrochloride, suloctidil, thioridazine hydrochloride, dichlorophen, saccharin and piroxicam, in combination with a polymyxin selected from colistin or polymyxin B or a pharmaceutically acceptable derivative thereof, for use in the treatment of a microbial infection, and in particular for killing clinically latent microorganisms associated with microbial infections. The invention also provides a combination comprising suloctidil or a pharmaceutically acceptable derivative or prodrug thereof, and a polymyxin selected from polymyxin E and polymyxin B or a pharmaceutically acceptable derivative thereof. This combination is particularly useful for the treatment and / or prevention of microbial infections.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application is a National Stage of International Application No. PCT / GB2015 / 054069 filed Dec. 18, 2015, claiming priorities based on British Patent Application Nos. 1422670.8, filed Dec. 18, 2014, 1500278.5, filed Jan. 8, 2015, and 1521901.7, filed Dec. 11, 2015, the contents of all of which are incorporated herein by reference in their entirety.BACKGROUND OF THE INVENTION[0002]The present invention relates to the use of certain known compounds in combination with an anti-microbial agent for the treatment of microbial infections. Additionally the present invention relates to the use of suloctidil or a pharmaceutically acceptable derivative or prodrug thereof in combination with polymyxin E or polymyxin B or a pharmaceutically acceptable derivative thereof for the treatment of microbial infections. In particular, it relates to the use of such combinations to kill multiplying and / or clinically latent microorganisms associated with micr...

AI Technical Summary

Benefits of technology

[0036]As described below, the combinations of the present invention have been demonstrated to be particularly effective against drug-resistant bacteria, particularly Gram-negative bacteria, opening the way for said combinations to be administered both to drug-resistant strains and in said strains before drug-resistance is built up, i.e. as a first line treatment.

[0053]It should be kept in mind that although a combination such as that claimed may initially be demonstrated to be functional in treating (M)DR strains, they can then be used in treating non-resistant strains. This is especially valuable in the context of the presently claimed combination where the primary therapy for Enterobacteriaceae, such as Escherichia coli, Klebsiella (e.g. Klebs. pneumoniae and Klebs. oxytoca) and Proteus (e.g. Pr. mirabilis, Pr. rettgeri and Pr. vulgaris) are anti-microbial drugs that are expensive due to prevailing patent protection. The replacement of such “ethical” drugs by a combination of “generic” antibiotics is thought to be beneficial from a therapeutic perspective as well as financial / economic perspective in times where governments are seeking to reduce the cost of healthcare.

Problems solved by technology

Before the introduction of antibiotics, patients suffering from acute microbial infections (e.g. tuberculosis or pneumonia) had a low chance of survival.

However, until the introduction of linezolid in 2000, there had been no new class of antibiotic marketed for over 37 years.

However, each of these types is characterised by its low rate of growth compared to log-phase bacteria under the same conditions.

However, dealing with “latent” bacteria by administering prolonged courses of antimicrobials poses its own problems.

For example, they may be viable but non-culturable; i.e. they cannot typically be detected by standard culture techniques, but are detectable and quantifiable by techniques such as broth dilution counting, microscopy, or molecular techniques such as polymerase chain reaction.

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